Identification of diagnostic and prognostic host biomarkers of Zika virus infection by transcriptome profiling

通过转录组分析鉴定寨卡病毒感染的诊断和预后宿主生物标志物

• 批准号: 9264796
• 负责人: Charles Yen Chiu
• 金额: $ 19.81万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-14 至 2018-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9264796
• 关键词: Acute; Acute Disease; Age; Americas; Antibody Specificity; Antibody titer measurement; Barbados; Biological Assay; Biological Markers; Blinded; Blood; Blood donor; Brazil; Caribbean region; Case Study; Clinical; Culicidae; Dengue; Diagnosis; Diagnostic; Diagnostic tests; Disease Outbreaks; Enrollment; Etiology; Evaluation; Falciparum Malaria; Fetal Development; Fetal Monitoring; Fever; Genes; Geography; Goals; Guillain-Barré Syndrome; Human; Immune response; Immunoglobulin M; Infection; Island; Laboratories; Lyme Disease; Microcephaly; Monitor; Mothers; Outcome; Paralysed; Patients; Pregnant Women; Reverse Transcriptase Polymerase Chain Reaction; Risk; Role; Saliva; Sampling; Serum; Specificity; Symptoms; Testing; Time; Transcript; Urine; Virus; Virus Diseases; Weight; Whole Blood; Woman; Zika Virus; adverse pregnancy outcome; base; brain abnormalities; chikungunya; differential expression; fetal; fetal infection; in utero; next generation sequencing; novel diagnostics; predict clinical outcome; pregnant; prognostic; screening; sex; specific biomarkers; transcriptome; transcriptome sequencing

PROJECT SUMMARY Identification of diagnostic and prognostic host biomarkers of Zika virus infection by transcriptome profiling There is currently an unprecedented ongoing outbreak of Zika virus (ZIKV) in the Americas, with more than 100,000 cases reported to date. Limitations to existing diagnostic tests include lack of specificity for antibody-based assays and a very narrow time window for PCR (<1 week). Better diagnostic tests are urgently needed to diagnose ZIKV infection. In addition, the weight of the combined evidence now shows that ZIKV is directly responsible for devastating adverse fetal outcomes in infected pregnant women, including in utero demise and microcephaly. There is currently no laboratory test to monitor infected women and assess their risk for fetal complications. Here we propose use transcriptome profiling analysis by RNA-Seq next-generation sequencing of blood, urine, and saliva samples from acutely infected patients to diagnose ZIKV infection, and of serially collected samples from ZIKV-infected pregnant women to monitoring the dynamics of the host response. The goal is to identify diagnostic and prognostic host biomarkers that may be correlated with active infection (for diagnosis) as well as fetal infection and outcomes in pregnant women, and that can be used to develop new assays for monitor ZIKV infection and disease.

项目摘要 应用转录组筛选寨卡病毒感染的诊断和预后宿主生物标志物 貌相 目前，寨卡病毒（ZIKV）在美洲正在爆发前所未有的疫情， 迄今为止报告的病例超过10万例。现有诊断测试的局限性包括缺乏特异性， 基于抗体的测定和非常窄的PCR时间窗（<1周）。更好的诊断测试迫在眉睫 需要诊断ZIKV感染。此外，综合证据的权重现在显示，ZIKV是 直接导致受感染孕妇的毁灭性不良胎儿结局，包括在子宫内 死亡和小头畸形目前还没有实验室检测来监测受感染的妇女并评估其 胎儿并发症的风险。在这里，我们建议使用RNA-Seq下一代转录组分析 对来自急性感染患者的血液、尿液和唾液样品进行测序以诊断ZIKV感染，以及 从ZIKV感染的孕妇中连续收集样品，以监测宿主的动态 反应目的是确定诊断和预后宿主生物标志物，可能与活性 感染（用于诊断）以及胎儿感染和孕妇的结局，并且可用于 开发用于监测ZIKV感染和疾病的新测定法。